ToxSci Advance Access originally published online on May 5, 2008
Toxicological Sciences 2008 104(2):332-340; doi:10.1093/toxsci/kfn085
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Neonatal Hypomyelination by the Herbicide 2,4-Dichlorophenoxyacetic Acid. Chemical and Ultrastructural Studies in Rats
* LATOEX, Facultad de Cs, Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina
Instituto de Biología Celular y Neurociencia, LANAIS-MIE, Facultad de Medicina, Universidad de Buenos Aires, Argentina
1 To whom correspondence should be addressed at Laboratorio de Toxicología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 531, (2000) Rosario, Prov, Santa Fe. Rep, Argentina. Fax: +54-341-4804598. E-mail: rduffard{at}fbioyf.unr.edu.ar.
Received February 22, 2008; accepted April 24, 2008
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Abstract |
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The purpose of this study was to determine whether 2,4-dichlorophenoxyacetic acid (2,4-D), which is an herbicide used to control the growth of broadleaf weeds, had a direct or an indirect (mediated by undernutrition) hypomyelinating effect. We also proposed to analyze the effect of 2,4-D on undernourished (UN) pups. Four experimental rat groups were used: well-nourished (WN) pups, litters with eight offsprings; UN pups, litters with fourteen offsprings; WN pups whose mother received 70 mg/kg/day of 2,4-D from postnatal day (PND) 9 to 21 (WN70 pups); and UN pups whose mother received 70 mg/kg/day of 2,4-D from PND 9 to 21 (UN70 pups). In this work, we demonstrated that (1) myelin proteins (analyzed by Western blot and/or immunohistochemical study) showed a significant decrease in WN70, UN, and UN70 with respect to control group; (2) there is a good correlation between these myelin-specific protein expression with the degree of myelin compaction detected by electron microscopy in groups exposed to 2,4-D; (3) a decreased and normal number of myelin sheets were detected in UN and 2,4-D exposed pups, respectively; and (4) undernourishment sensitized pups to the hypomyelinating effect of 2,4-D. According to this and besides the fact that WN70 group have no body weight changes, these results are indicating that 2,4-D and undernourishment are two independent hypomyelinating factors.
Key Words: 2,4-dichlorophenoxyacetic acid; herbicide; brain development; myelin proteins; myelin ultrastructure; neurotoxicity; neonate rat.